Individualized decitabine dosing for post-HSCT maintenance in MDS and secondary AML from MDS: long-term outcomes from the PODAC trial and matched controls.

[BACKGROUND] Relapse after allogeneic hematopoietic stem cell transplantation (HSCT) remains a major clinical challenge in higher-risk myelodysplastic neoplasms (MDS). Although hypomethylating agents have been evaluated as posttransplant maintenance therapy, their efficacy remains uncertain.

[OBJECTIVE] We aimed to evaluate the long-term clinical outcomes of individualized decitabine maintenance therapy following HSCT in patients with MDS or secondary acute myeloid leukemia from MDS.

[DESIGN] This was a retrospective comparative study based on a long-term follow-up of the phase I PODAC trial, which individualized posttransplant decitabine maintenance dosing.

[METHODS] Nineteen PODAC participants were included in the treatment group and compared with 52 matched control patients selected through target trial emulation using identical eligibility criteria.

[RESULTS] For the 19 PODAC participants, a median of 6 cycles was administered, starting at 5 mg/m/day and escalating to a median maintenance dose of 7 mg/m/day. After a median follow-up of 11.4 years in the PODAC group and 9.7 years in the control group ( = 0.90), no significant differences were observed between the two groups in overall survival, relapse-free survival, graft-versus-host disease (GVHD)-free relapse-free survival, or the incidence of relapse, nonrelapse mortality, and grades II-IV acute GVHD. However, the incidence of moderate-to-severe chronic GVHD was significantly lower in the PODAC group and decitabine maintenance emerged as an independent predictor for longer chronic GVHD-free relapse-free survival (cCRFS).

[CONCLUSION] Decitabine maintenance using an adaptive dosing approach enabled prolonged treatment and was associated with a lower incidence of chronic GVHD and improved cGRFS. However, it did not improve survival or relapse outcomes compared to the control group.